Hypoadiponectinemia and the presence of metabolic syndrome in patients with chronic kidney disease: results from the KNOW-CKD study.

BACKGROUND: In patients with chronic kidney disease, metabolic syndrome has been demonstrated to be the culprit behind diverse complications. Adiponectin is known to have anti-atherogenic and cardio-protective effects. Meanwhile, the relationship between adiponectin and metabolic syndrome in patients with chronic kidney disease has not been clarified. The aim of this study was to elucidate the relationship between adiponectin level and metabolic syndrome in patients with chronic kidney disease. METHODS: The KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease is a cohort study that enrolled subjects with chronic kidney disease throughout South Korea. From February 2011 to July 2014, data were collected from 1332 patients with chronic kidney disease. RESULTS: The mean age of the patients was 53.5 years and 803 patients (60.7%) were men. The median adiponectin level was 10.7 µg/mL and 585 (44.3%) patients had metabolic syndrome. In multiple linear regression analysis, log adiponectin was positively associated with high-density lipoprotein cholesterol levels (ß = 0.006), whereas it was negatively associated with serum albumin (ß = -0.284), triglyceride (log ß = -0.288), high sensitivity C-reactive protein (log ß = -0.058) levels and estimated glomerular filtration rate (ß = -0.005). Multiple logistic regression analysis indicated that low adiponectin level was independently associated with a higher risk of metabolic syndrome (per 1 µg/mL increase; odds ratio = 0.953, 95% confidence interval = 0.898-0.970, P < 0.001) after adjustment for multiple confounding factors. CONCLUSIONS: Hypoadiponectinemia is independently associated with the presence of metabolic syndrome in patients with chronic kidney disease.

Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study.

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: ß=0.263, p<0.001; age: ß=0.122, p=0.010; ESA dose: ß=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study.

BACKGROUND: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. METHODS: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. RESULTS: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). CONCLUSION: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

Irisin, a novel myokine is an independent predictor for sarcopenia and carotid atherosclerosis in dialysis patients.

OBJECTIVE: In end-stage renal disease, deleterious effect of sarcopenia on cardiovascular disease has been explained mainly by chronic inflammation. However, evidence emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we sought to investigate the effect of irisin, a recently introduced myokine, on the association between sarcopenia and cardiovascular disease in peritoneal dialysis (PD) patients. METHODS: Serum irisin concentrations were assessed by enzyme-linked immunosorbent assay in 102 prevalent PD patients and 35 age- and sex-matched controls. To determine sarcopenia and cardiovascular disease, anthropometric indices including mid-arm muscle circumference (MAMC) and carotid intima-media thickness (cIMT) were measured. RESULTS: Serum irisin concentrations were significantly lower in PD patients than in controls (184.2 ± 88.0 vs. 457.2 ± 105.5 ng/mL, P < 0.001). In PD patients, univariate linear regression analysis showed that serum irisin was positively correlated with MAMC and thigh circumference, but negatively correlated with residual renal function and cIMT. Multivariate analysis revealed that MAMC (per 1 cm increase, B = 8.78, 95% confidence interval [CI] = 0.77-16.79, P = 0.03) had an independent association with serum irisin. In addition, serum irisin was a significant independent predictor for carotid atherosclerosis even after adjustment for high-sensitivity C-reactive protein in PD patients (per 1 g/mL increase, odds ratio = 0.990, 95% CI = 0.982-0.997, P = 0.007). CONCLUSION: This study demonstrated that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in PD patients. Additional studies to provide a confirmation and examine possible mechanisms are warranted.

An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock.

INTRODUCTION: Mean platelet volume (MPV) is suggested as an index of inflammation, disease activity, and anti-inflammatory treatment efficacy in chronic inflammatory disorders; however, the effect of MPV on sepsis mortality remains unclear. Therefore, we investigated whether the change in MPV between hospital admission and 72 hours (ΔMPV72h-adm) predicts 28-day mortality in severe sepsis and/or septic shock. METHODS: We prospectively enrolled 345 patients admitted to the emergency department (ED) who received standardized resuscitation (early goal-directed therapy) for severe sepsis and/or septic shock between November 2007 and December 2011. Changes in platelet indices, including ΔMPV72h-adm, were compared between survivors and non-survivors by linear mixed model analysis. The prognostic value of ΔMPV72h-adm for 28-day mortality was ascertained by Cox proportional hazards model analysis. RESULTS: Thirty-five (10.1%) patients died within 28 days after ED admission. MPV increased significantly during the first 72 hours in non-survivors (P = 0.001) and survivors (P < 0.001); however, the rate of MPV increase was significantly higher in non-survivors (P = 0.003). Nonetheless, the difference in the platelet decline rate over the first 72 hours did not differ significantly between groups (P = 0.360). In multivariate analysis, ΔMPV72h-adm was an independent predictor of 28-day mortality, after adjusting for plausible confounders (hazard ratio, 1.44; 95% confidence interval, 1.01-2.06; P = 0.044). CONCLUSIONS: An increase in MPV during the first 72 hours of hospitalization is an independent risk factor for adverse clinical outcomes. Therefore, continuous monitoring of MPV may be useful to stratify mortality risk in patients with severe sepsis and/or septic shock.

LDL cholesterol affects clinical outcomes in incident hemodialysis patients during the early stages of dialysis.

BACKGROUND/AIMS: Using a cohort of incident hemodialysis (HD) patients, this study investigated the impact of lipid profiles on clinical outcomes, especially in the early period of dialysis. METHODS: A prospective cohort of 867 incident HD patients was selected. In order to determine the impact of cholesterol level on primary outcome, Cox regression analyses were performed for LDL and non-HDL (NHDL) variables. RESULTS: Univariate analysis revealed an increase in primary outcome risk with an LDL cholesterol level of 100 mg/dl or higher compared to an LDL cholesterol level lower than 100 mg/dl. High LDL cholesterol remained a significant independent predictor of the composite outcome, even after adjusting for age, gender, diabetes mellitus, preexisting CV disease, albumin, and hs-CRP. CONCLUSION: Serum LDL cholesterol at the time of HD commencement was a significant independent risk factor for the composite outcome of all-cause mortality and CV events in incident HD patients during the early stages of dialysis.

Hyponatremia as a predictor of mortality in peritoneal dialysis patients.

BACKGROUND AND AIM: Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients. METHODS: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients. RESULTS: Among the baseline parameters, serum sodium level was positively associated with serum albumin (ß = 0.145; p = 0.003) and residual renal function (RRF) (ß = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (ß = -0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73-0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70-0.85; p<0.001) deaths. CONCLUSIONS: This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately.

Optimal proteinuria target for renoprotection in patients with IgA nephropathy.

BACKGROUND: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. METHODS: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. RESULTS: During a median follow-up duration of 65 (12-154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3-0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0-2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0-2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3-0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (-0.41±1.68 vs. -0.73±2.82 ml/min/1.73 m2/year, P = 0.03). CONCLUSION: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3-0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.

Clinical features and outcomes of focal segmental glomerulosclerosis pathologic variants in Korean adult patients.

BACKGROUND: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. METHODS: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.

Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

Comparison of the Haas and the Oxford classifications for prediction of renal outcome in patients with IgA nephropathy.

Pathologic features can provide valuable information for determining prognosis in IgA nephropathy (IgAN). However, it is uncertain whether the Oxford classification, a new classification of IgAN, can predict renal outcome better than previous ones. We conducted a retrospective cohort study in 500 patients with biopsy-proven IgAN between January 2002 and December 2010 to compare the ability of the Haas and the Oxford classifications to predict renal outcome. Primary outcome was a doubling of the baseline serum creatinine concentration (D-SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D-SCr and end-stage renal disease, respectively. There were graded increases in the development of D-SCr in the higher Haas classes. In addition, the primary endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than those without such lesions. In multivariate Cox regression analyses, the Haas class V (HR, 12.19; P=.002) and the Oxford T1 (hazard ratio [HR], 6.68; P<.001) and T2 (HR, 12.16; P<.001) lesions were independently associated with an increased risk of reaching D-SCr. Harrell's C index of each multivariate model with the Haas and the Oxford classification was 0.867 (P=.015) and 0.881 (P=.004), respectively. This was significantly higher than that of model with clinical factors only (C=0.819). However, there was no difference in C-statistics between the 2 models with the Haas and the Oxford classifications (P=.348). This study suggests that the Haas and the Oxford classifications are comparable in predicting progression of IgAN.

Effect of peritoneal dialysis modality on the 1-year rate of decline of residual renal function.

PURPOSE: The effect of different peritoneal dialysis (PD) modalities on the decline in residual renal function (RRF) is unclear due to inconsistencies among studies. In particular, the effect of automated peritoneal dialysis (APD) modalities [continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD)] on RRF has not been examined in a large cohort. MATERIALS AND METHODS: We conducted a single-center retrospective study to investigate the association between PD modalities and decline in RRF in 142 incident PD patients [34 on CCPD, 36 on NIPD, and 72 on continuous ambulatory peritoneal dialysis (CAPD)]. RRF was measured within 2 months from PD start and at 1 year after PD initiation. RESULTS: The RRF at 1 year after PD initiation was 1.98±2.20 mL/min/1.73 m² in CCPD patients and 3.63±3.67 mL/min/1.73 m² in NIPD patients, which were moderately lower than 4.23±3.51 mL/min/1.73 m² in CAPD patients (p=0.064). Moreover, there was no significant difference in the 1-year rate of decline of RRF between CCPD and NIPD patients, although APD patients had a faster 1-year RRF decline rate than CAPD patients (CCPD and NIPD vs. CAPD: -45.68 and -36.69 vs. 1.17%/year, p=0.045). APD was associated with a more rapid decline in RRF in patients with end-stage renal disease undergoing PD, although multivariate analysis attenuated the significance of this finding (ß=-31.50; 95% CI, -63.61 to 0.62; p=0.052). CONCLUSION: Our results suggest that CAPD might be more helpful than APD for preserving RRF during the first year of dialysis therapy, although there was no significant difference in the 1-year rate of decline of RRF between the two APD modalities.

Urine output is associated with prognosis in patients with acute kidney injury requiring continuous renal replacement therapy.

PURPOSE: Although some studies have found that early initiation of continuous renal replacement therapy (CRRT) is associated with better prognosis, no consensus exists on the best timing to start CRRT. We investigated whether the timing of CRRT initiation was relevant to overall mortality and explored which factors at the time of CRRT initiation were associated with better outcomes in critically ill patients with acute kidney injury (AKI). MATERIALS AND METHODS: A total of 361 patients who received CRRT for AKI between 2009 and 2011 were collected and divided into 2 groups based on the median blood urea nitrogen (BUN) levels or 6-hour urine output immediately before CRRT was started. The impact of the timing of CRRT initiation stratified by BUN concentration or urine output on 28-day all-cause mortality was compared between groups. RESULTS: When the timing of CRRT initiation was stratified by 6-hour urine output, 28-day all-cause mortality rates were significantly lower in the nonoliguric group compared with the oliguric group (P = .02). In contrast, clinical outcomes were not different between the low-BUN and the high-BUN groups (P = .30). Cox regression analysis revealed that 28-day all-cause mortality risk was significantly lower in the nonoliguric group stratified by 6-hour urine output, even after adjusting for age, sex, mean arterial pressure, Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and serum biomarkers (hazard ratio, 0.85; 95% confidence interval, 0.65-0.99; P = .04). CONCLUSIONS: Urine output but not BUN concentration was significantly associated with a better prognosis in critically ill patients with AKI requiring CRRT.

Early experience using a left atrial appendage occlusion device in patients with atrial fibrillation.

PURPOSE: Atrial fibrillation (AF) is one of the major risk factors for ischemic stroke, and 90% of thromboembolisms in these patients arise from the left atrial appendage (LAA). Recently, it has been documented that an LAA occlusion device (OD) is not inferior to warfarin therapy, and that it reduces mortality and risk of stroke in patients with AF. MATERIALS AND METHODS: We implanted LAA-ODs in 5 Korean patients (all male, 59.8 ± 7.3 years old) with long-standing persistent AF or permanent AF via a percutaneous trans-septal approach. RESULTS: 1) The major reasons for LAA-OD implantation were high risk of recurrent stroke (80%), labile international neutralizing ratio with hemorrhage (60%), and 3/5 (60%) patients had a past history of failed cardioversion for rhythm control. 2) The mean LA size was 51.3 ± 5.0 mm and LAA size was 25.1 × 30.1 mm. We implanted the LAA-OD (28.8 ± 3.4 mm device) successfully in all 5 patients with no complications. 3) After eight weeks of anticoagulation, all patients switched from warfarin to anti-platelet agent after confirmation of successful LAA occlusion by trans-esophageal echocardiography. CONCLUSION: We report on our early experience with LAA-OD deployment in patients with 1) persistent or permanent AF who cannot tolerate anticoagulation despite significant risk of ischemic stroke, or 2) recurrent stroke in patients who are unable to maintain sinus rhythm.

Postoperative malignant hyperthermia: an analysis of cases from the North American Malignant Hyperthermia Registry.

BACKGROUND: The initial presentation of malignant hyperthermia (MH) may begin in the postoperative period. However, the maximal latency period between the end of anesthesia care and the onset of postoperative MH is unknown. The authors hypothesized that this latency period is short and is not manifested by hyperthermia as the initial presenting sign. The authors sought to test this hypothesis and to describe the clinical characteristics of postoperative MH by analysis of suspected cases in the North American Malignant Hyperthermia Registry. METHODS: Of 528 possible or suspected cases of MH in the North American Malignant Hyperthermia Registry, the authors identified 64 possible reports of postoperative MH. The records were reviewed in detail by the authors, each of whom assigned a qualitative score of "likely," "not likely," "not enough information available," or "not applicable" (where MH was not the final definitive diagnosis). Postoperative MH was confirmed after a consensus meeting of the three senior authors who reviewed in detail all possible "likely" cases. RESULTS: The authors identified postoperative MH in 10 subjects. All received volatile agents and 5 also received succinylcholine. All demonstrated signs characteristic of acute MH, including generalized rigidity, hypercapnia and/or tachypnea, tachycardia, and hyperthermia. No subject demonstrated hyperthermia as the presenting sign. The latency period between the anesthesia finish time and the onset of a sign indicative of acute MH ranged from 0 to 40 min. CONCLUSIONS: Postoperative MH is uncommon, occurring in 10 of 528 suspected MH cases (1.9%) reported to the North American Malignant Hyperthermia Registry. Postoperative MH began shortly after completion of the anesthetic care. Hyperthermia was not a presenting sign of MH.